BK Polyomavirus Nephropathy in Kidney Transplantation: Balancing Rejection and Infection.

BK polyomavirus nephropathy (BKVN) and allograft rejection are two closely-associated diseases on opposite ends of the immune scale in kidney transplant recipients. The principle of balancing the immune system remains the mainstay of therapeutic strategy. While patient outcomes can be improved through screening, risk factors identification, and rapid reduction of immunosuppressants, a lack of standard curative therapy is the primary concern during clinical practice. Additionally, difficulty in pathological differential diagnosis and clinicopathology's dissociation pose problems for a definite diagnosis. This article discusses the delicate evaluation needed to optimize immunosuppression and reviews recent advances in molecular diagnosis and immunological therapy for BKVN patients. New biomarkers for BKVN diagnosis are under development. For example, measurement of virus-specific T cell level may play a role in steering immunosuppressants. The development of cellular therapy may provide prevention, even a cure, for BKVN, a complex post-transplant complication.

Tacrolimus Blood Level Fluctuation Predisposes to Coexisting BK Virus Nephropathy and Acute Allograft Rejection.

BK virus nephropathy (BKVN) and allograft rejection are two distinct disease entities which occur at opposite ends of the immune spectrum. However, they coexist in renal transplant recipients. Predisposing factors for this coexistence remain elusive. We identified nine biopsy-proven BKVN patients with coexisting acute rejection, and 21 patients with BKVN alone. We retrospectively analyzed the dosage and blood concentrations of immunosuppressants during the 3-month period prior to the renal biopsy between the two patient groups. Compared to the BKVN alone group, renal function was noticeably worse in the coexistence group (p = 0.030). Regarding the dose and average drug level of immunosuppressants, there was no difference between the two groups. Interestingly, the coefficient of variance of tacrolimus trough blood level was noticeably higher during the 3-month period prior to the renal biopsy in the coexistence group (p = 0.010). Our novel findings suggest that a higher variability of tacrolimus trough level may be associated with the coexistence of BKVN and acute rejection. Since the prognosis is poor and the treatment is challenging in patients with coexisting BKVN and acute rejection, transplant clinicians should strive to avoid fluctuations in immunosuppressant drug levels in patients with either one of these two disease entities.

Interaction between geriatric nutritional risk index and decoy receptor 3 predicts mortality in chronic hemodialysis patients.

BACKGROUND: Protein-energy wasting (PEW) is common and associated with poor outcome in hemodialysis patients. In hemodialysis patients, geriatric nutritional risk index (GNRI) and decoy receptor 3 (DcR3) have been shown as the nutritional and inflammatory markers, respectively. The present study aimed to assess the predictive ability of GNRI and DcR3 for PEW status and long-term outcomes in chronic hemodialysis patients. METHODS: A prospective cohort of 318 hemodialysis patients was conducted with a median follow-up of 54 months. Malnutrition-inflammation score (MIS) was used as the reference standard for the presence of PEW. Endpoints were cardiovascular and all-cause mortality. RESULTS: Baseline GNRI had a strong negative correlation with DcR3 and MIS score. For patients with age < or ≥60, high DcR3 and low GNRI were independent predictors for the presence of PEW at baseline. At the end of the study, 81 patients died (27 cardiovascular deaths). The adjusted hazard ratios (95% confidence intervals) of low GNRI and high DcR3 were 1.93 (1.1-4.8) and 2.53 (1.2-5.5) for cardiovascular mortality and 1.85 (1.1-3.2) and 2.37 (1.5-3.7) for all-cause mortality, respectively. While integrated into a model of conventional risk factors, GNRI together with DcR3 further significantly improved the predictability for overall mortality (c statistic, 0.823). CONCLUSIONS: Low GNRI and high DcR3 were the alternatives for identifying hemodialysis patients at risk of PEW and overall mortality. Further studies are needed to verify whether timely recognition of hemodialysis patients with a high malnutrition-inflammation risk could reduce their mortality by appropriate interventional strategies.

Impact of thyroid dysfunction on erythropoietin dosage in hemodialysis patients.

BACKGROUND: Although thyroid diseases exist in patients with renal failure, thyroid function tests are not routine tests in patients on chronic hemodialysis (HD). Therefore, the impact of thyroid diseases on erythropoietin (EPO) dosage in HD patients is not well defined. This study evaluated the relationship between the dose of EPO and the presence or absence of thyroid dysfunction in HD patients. METHODS: This study included 1013 adult patients on HD who did not have a malignancy, liver cirrhosis, thalassemia, iron deficiency, gastrointestinal bleeding, or a major operation within 6 months. Patients were characterized as being euthyroid, or having the sick euthyroid syndrome, primary hypothyroidism, subclinical hypothyroidism, hyperthyroidism, or subclinical hyperthyroidism based on thyroid function tests. Routine biochemistry profiles including an index of the efficiency of HD, along with clinical data over the previous 6-month period, were collected and analyzed. Multiple regression models were employed to assess the relationship between the dose of EPO and the presence or absence of thyroid status. RESULTS: The mean monthly EPO dosages were 77.7±37.0, 70.2±40.6, 90.8±68.4, 78.5±46.7, and 82.3±41.2 µg, respectively, in the sick euthyroid syndrome, euthyroid patients, hypothyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism groups (p<0.05). After adjustment of all other variables in multiple regression, the mean monthly EPO dosage was 19.00±8.59 µg more in hypothyroid patients compared with euthyroid patients (p=0.027). Further, considering an interaction with the presence of diabetes, the mean monthly EPO dosage in patients with either hypothyroidism or subclinical hypothyroidism and diabetes was 54.66±17.12 µg (p=0.001) and 31.51±10.38 µg more than that of euthyroid patients, respectively (p=0.002). CONCLUSIONS: In HD patients, the EPO dosage required to maintain the target hemoglobin level is significantly higher in patients having both hypothyroidism or subclinical hypothyroidism and diabetes than in euthyroid patients.